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Per Wester

Publications and source records attributed to Per Wester.

10 recordsLinked to original sources

Establishing a photothrombotic 'ring' stroke model in adult mice with late spontaneous reperfusion: quantitative measurements of cerebral blood flow and cerebral protein synthesis.

This study sought to establish the photothrombotic 'ring' stroke model with late spontaneous reperfusion in adult mice. By applying a 3.0-mm diameter laser ring-beam (514 nm, 0.21 mm thick, 0.65 W/cm2) onto the exposed skull for 60 secs with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15 secs, the centrally located cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit. In this region, local cerebral blood flow (lCBF) measured by laser-Doppler flowmetry declined promptly after irradiation to 43% of the baseline value at 30 mins poststroke. Using double tracer autoradiography, quantitative lCBF measured with [14C]iodoantipyrine was 46 to 17 to 58 ml/100 g/mins at 4 h to 48 h to 7 days postischemia in this area. Cerebral protein synthesis (CPS), as detected by [3H]leucine incorporation into protein, transiently decreased to 57% to 38% to 112% at 4 h to 48 h to 7 days postischemia in the center region. Morphologically, some neurons in the center region appeared swollen at 4 h. At 48 h, the majority of neurons were severely swollen with eosinophilia and pyknosis, whereas at 7 days poststroke' the tissue morphology became partly restored. The center within the mouse photothrombotic ring lesion thus exhibits reversible alterations of local CBF, CPS and tissue morphology that are reminiscent of the cortical penumbra in other models of focal cerebral ischemia.

Animals↗

[Thrombolytic therapy in acute ischemic stroke. Critical analysis of current knowledge].

Thrombolysis is a highly promising treatment in acute ischaemic stroke. There is evidence of positive effects at least up to three hours and most probably up to six. The risk of intracranial haemorrhage is increased fourfold with thrombolysis; risk factors other than the treatment as such have not been identified for certain; the risk is not related to giving thrombolysis during the 0-3 as opposed to the 3-6 hour time window. There is a non-significant excess of deaths, ranging from a small reduction to a substantial excess. There is not enough evidence to answer several questions regarding the influence of patient- and stroke characteristics on effectsize; death; and risk of intracranial haemorrhage. Giving priority to new large randomized controlled trials is essential to achieve this knowledge.

Acute Disease↗

Characterization of a novel chronic photothrombotic ring stroke model in rats by magnetic resonance imaging, biochemical imaging, and histology.

A novel photothrombotic ring stroke model was characterized by multiparametric magnetic resonance imaging, imaging of cerebral blood flow (CBF), adenosine triphosphate (ATP), pH, and histology. Ischemia was initiated by transosseous irradiation of a predefined brain area intravenously perfused by the photosensitive dye erythrosin B in male Wistar rats. In the region of the primary ring-lesion, the phototoxic reaction caused necrosis reflected by low relative ATP levels (28 +/- 15%), alkalosis (pH: 7.35 +/- 0.50), and histologic evidence at 14 days after lesion induction. In the ring-encircled interior region (region-at-risk), spontaneous tissue reperfusion (relative CBF: 93 +/- 3%) enabled partial tissue preservation. This was demonstrated by a less impaired energy metabolism (ATP: 65 +/- 23%), normal pH (7.01 +/- 0.50), and still normal cellular structures shown by histologic staining. Analysis of the temporal characteristics within the region-at-risk revealed a slow continuous increase of the apparent diffusion coefficient of water (ADC) to 144 +/- 16% of control (14d) and an early vasogenic edema, reflected by an increase of the T2 relaxation time to 143 +/- 17% of control (2d). Both final ADC and T2 correlated well with the tissue pH within the region-at-risk, thus emphasizing the usefulness of this multiparametric noninvasive imaging approach.

Adenosine Triphosphate↗

Dynamic changes of the anti- and pro-apoptotic proteins Bcl-w, Bcl-2, and Bax with Smac/Diablo mitochondrial release after photothrombotic ring stroke in rats.

The anti-apoptotic proteins Bcl-w and Bcl-2 and the pro-apoptotic protein Bax may mediate cell death or survival via regulation of the mitochondria including second mitochondria-derived activator of caspase (Smac)/direct inhibitor of apoptosis protein (IAP)-binding protein with low pI (DIABLO) release. This study aimed to explore alterations in Bcl-w, Bcl-2, and Bax and the relationship between these proteins and Smac/DIABLO by means of in situ hybridization, immunohistochemical (IHC) staining, and Western blots after low- and high-intensity photothrombotic ring stroke. At 4 h after low-intensity irradiation, we found widespread bcl-w overexpression on both the mRNA and protein levels in the bilateral cortex except the ring lesion region and in subcortical regions. A prolonged elevation of Bcl-2 with relatively unchanged Bax in the mitochondrial fraction was demonstrated from 4 to 72 h. These upregulated anti-apoptotic proteins combined with little Smac/DIABLO release might be associated with increased cell survival and thereby remarkable morphological recovery after low-intensity irradiation. After high-intensity irradiation, we observed decreased bcl-w and bcl-2 mRNA with increased Bcl-2 protein in the cytosolic fraction, whereas the Bax protein remained in scattered ischaemic cells in the ring lesion and the region at risk that corresponded with release of Smac/DIABLO from mitochondria to the cytosol at 1-24 h. These changes might be related to the massive cell death observed after high-intensity irradiation. Taken together, the balance and the location of anti-apoptotic proteins vs. pro-apoptotic proteins could be associated with the translocation of Smac/DIABLO from the mitochondria to the cytosol and therefore closely related to cell death or survival after focal cerebral ischaemia.

Animals↗

["Brain attack"--care during the acute phase is crucial for the long term outcome].

Brain attack should be considered as an urgent condition, comparable with acute coronary syndrome. It is important that patients with an evolving stroke should seek medical attention at a hospital as soon as possible in order to receive thrombolysis for a few, to elucidate complicating conditions and to get access to stroke unit care. The Scandinavian model with non-intensive stroke units and coordinated continuously educated multidisciplinary teams with immediate mobilisation and early rehabilitation reduces death, dependency and required in-hospital days. These positive effects are independent of patient's age, sex or degree of brain damage. Attempts to reduce the extent of brain damage with neuroprotectants have so far been without success, some future strategies test the effects of combined thrombolysis and neuroprotectants. There is evidence that acute stroke patients should be monitored regularly during the acute phase aiming at normalized physiological conditions. This means that hypoxemia, dehydration, hyperthermia, hyperglycemia and hypotension should be prevented and if occurring, promptly corrected.

Emergency Medical Services↗

[New treatment modalities for stroke in the near future].

The ischemic penumbra is a functionally depressed, structurally intact but potentially salvageable region in the brain following stroke. Several pathophysiological mechanisms dominate during various intervals after stroke onset. New promising clinical treatment possibilities include hemicraniectomy in younger patients with malignant media infarction (albeit no RCT data available as today); brain cooling during the acute phase; and constraint-induced therapy and physiotherapy enhanced either by psychotomimetics (amphetamine) to improve general function or by anesthesia of the shoulder and upper arm to improve chronic paretic hand function. In a further future perspective, promising results from animal experiments should be clinically translated. Such results include newborn neurons induced in the penumbra spontaneously after stroke (endogenous neurogenesis) or exogenously administered stem cells implanted directly, or alternatively migrating to the ischemic penumbra, where differentiation to functional neurons is hoped for. Several safety aspects are however crucial, especially with regard to minimizing the risk of tumorigenesis after application of exogenous stem cells, and further detailed experimental characterization is essential before large scale clinical trials are initiated.

Acute-Phase Reaction↗

Real-time cortical cerebral blood flow follow-up in conscious, freely moving rats by laser Doppler flowmetry.

This article describes a laser Doppler flowmetry (LDF) system that enables repeated measurements and thereby long-term followup of cortical cerebral blood flow (CBF) in awake and freely moving rats. The system consists of a specially designed flow probe adapter, a flow probe connector, and a LDF flow probe, which may thereby rotate through its own axis. During the experiment, the flow adapter is permanently mounted onto the rat's skull bone. A thin layer of skull bone is left intact at the site for cortical CBF measurements. The probe connector and the flow probe may be repeatedly detached and remounted to the adapter, which allows for cortical cerebral blood flow recording from exactly the same anatomical location. The laser Doppler flowmetry system enables stable cortical CBF recordings in the conscious rat while it moves freely in a bowl cage.

Animals↗

Long-lasting neuronal apoptotic cell death in regions with severe ischemia after photothrombotic ring stroke in rats.

Apoptotic and necrotic cell death may act in concert in focal cerebral ischemia. This study explored the temporal and spatial pattern of apoptosis and necrosis in a novel photothrombotic ring stroke model with or without spontaneous reperfusion. Adult male Wistar rats were subjected to a ring-shaped laser irradiation beam simultaneously with intravenous erythrosin B infusion. The presence and attributes of apoptosis and necrosis in the anatomically well-defined cortical region at risk and ring-lesion region were verified under light microscopy with TUNEL, Hoechst 33342, and hematoxylin and eosin staining. Cells exhibiting apoptotic morphology with chromatin condensation and apoptotic bodies and necrotic ghost appearance were observed. The occurrence of apoptosis and necrosis in the ischemic regions was confirmed by electron microscopy and gel electrophoresis, in which DNA isolated from the lesion area revealed both a ladder and a smear. Double staining with TUNEL and the cell markers NeuN, glial fibrillary acidic protein, and ED-1 revealed that the majority of apoptotic cells were of neuronal origin. Cells exhibiting pyknosis/eosinophilia, apoptosis, or ghost appearance were quantified by stereological means. In subregions with severe ischemia, the peak appearance of apoptotic cells started earlier, i.e., at 24 h, than the peak of necrotic cells, and the high concentration of the apoptotic cells remained as long as that of necrotic cells, i.e., until 72 h post-ischemia. The ratio of apoptotic to necrotic cells was approximately 1:2. Therefore, apoptosis may be an important contributor to neuronal cell death in brain regions with severely reduced blood flow after thrombo-embolic stroke.

Animals↗